Abstract 182: Inhibitor of differentiation (Id)3 Regulation of the Vasculature in Adipose Tissue
Rationale: Over half of the U.S. is overweight or obese and excessive weight gain greatly increases one’s risk of cardiovascular disease. Adipose tissue requires new blood vessel formation to support transport of nutrients during expansion. Our lab has previously published that global loss of the helix-loop-helix transcription factor Inhibitor of differentiation 3 (Id3) results in attenuated increases in adipose depot size and microvascular blood volume in mice fed a high fat diet (HFD). Id3 has also been implicated in regulating tumor angiogenesis. Together, our results suggest that Id3 is regulating HFD-induced angiogenesis in adipose tissue. Methods and Results: To determine if Id3 is regulating angiogenesis, we performed genetic, cellular, and arterial experiments and analyses. Using bromodeoxyuridine (BrdU) treatments and flow cytometry, we found that endothelial cells within adipose tissue of mice with a global genetic knockout of Id3 (Id3 KO) had fewer proliferating (BrdU-positive) endothelial cells (0.0679% BrdU+CD31+ cells) than wild type (WT) mice (0.754% BrdU+CD31+). Using mouse adipose tissue gene expression data from the Gene Ontology Consortium database, we found that genes correlating most significantly with Id3 were functionally classified under categories of vascular development (p = 4.45E-8, correlation significance) and angiogenesis (p = 1.66E-6). Sox18, a known transcriptional regulator of blood vessel formation, shows higher relative gene expression in Id3 WT (1.42 ± 0.417) than Id3 KO (0.332 ± 0.126) adipose tissue. Finally, preliminary findings using pressure myography demonstrate that Id3 KO mice have a higher baseline arterial diameter than Id3 WT. Conclusion: Dysregulation of vascular development during adipose tissue expansion is altering arterial function in an Id3-dependent manner.